Cancer du sein : recommandations sur l’usage de la phytothérapie

Many women being treated for breast cancer turn to phytotherapy, notably to prevent the side effects of the cancer treatments. This practice is based on tradition, sometimes backed up by pharmacological studies, rarely on clinical studies. As medicinal plants can be toxic or interact with medicines, pharmacists and chemotherapists must assess the risk-benefit ratio

Plantes médicinales et cancer du sein (état des lieux et recommandations sur leurs utilisations)

Les traitements anticancéreux et notamment ceux pris par voie orale peuvent être à l origine d effets indésirables qui perturbent la qualité de vie de la patiente. L homéopathie, la phytothérapie, l acupuncture apparaissent parfois comme des solutions pour la patiente. Le recours à ces pratiques non conventionnelles est désigné sous le terme de médecines alternatives et complémentaires. Depuis quelques années, en cancérologie, l attrait des patientes pour ces dernières n a fait qu accroitre. Nous avons effectué une étude concernant le recours aux médecines complémentaires chez des patientes atteintes d un cancer du sein dans un service d hospitalisation de jour à l Institut de Cancérologie de l Ouest Paul Papin (ICO Paul Papin) d Angers. De plus en plus de patientes emploient des produits à base de plantes considérant que, puisqu ils sont naturels, ils sont inoffensifs. Cependant, les plantes médicinales peuvent comporter des contre-indications, interagir avec les médicaments conventionnels et même provoquer des effets secondaires et des toxicités. Nous avons élaboré des outils destinés aux patientes et aux professionnels de santé qui synthétisent l ensemble des recommandations faites sur les plantes médicinales étudiées. De plus en plus de preuves scientifiques viennent étayer l efficacité des plantes médicinales sous certaines conditions d utilisation. Malgré cela, de nombreuses lacunes restent à combler en ce qui concerne leur innocuité. C est pourquoi, dans l attente de données scientifiques complémentaires nous recommandons aux patientes qui souhaitent consommer des plantes médicinales d aborder cette utilisation avec les professionnels de santé impliqués dans leur prise en charge.Anticancer treatments including those taken orally can cause side effects interfering on the patient s life quality. Homeopathy, herbal medicine, acupuncture may be in some cases possible alternative solutions for the patient. The use of these unconventional practices is referred to as complementary and alternative medicines. In the past few years, the patients interest for these medicines is increasing. We conducted a study on the use of complementary medicine for women suffering of breast cancer. This study took place in a day-care hospital in Angers: ICO Paul Papin. More and more patients use herbal products, because they are natural and they think that they are harmless. However, medicinal plants may have contraindications and may interact with conventional drugs and even cause side effects or be toxic. We have developed tools for patients and healthcare professionals that summarize all the recommendations about medicinal plants already studied. More and more scientific evidence support the efficiency of medicinal plants under specific conditions. However many aspects have to be clarified regarding their safety. Therefore, pending further scientific data we recommend that patients who wish to consume medicinal plants get close to their healthcare professionals to check the relevance of this decision and its possible impacts.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Zinc and diabetes

Zn(2+) ions are essential for the normal processing and storage of insulin and altered pancreatic insulin content is associated with all forms of diabetes mellitus. Work of the past decade has identified variants in the human SLC30A8 gene, encoding the zinc transporter ZnT8 which is expressed highly selectively on the secretory granule of pancreatic islet β and α cells, as affecting the risk of Type 2 Diabetes. Here, we review the regulation and roles of Zn(2+) ions in islet cells, the mechanisms through which SLC30A8 variants might affect glucose homeostasis and diabetes risk, and the novel technologies including recombinant targeted zinc probes and knockout mice which have been developed to explore these questions

Changes in the expression of the type 2 diabetes-associated gene VPS13C in the β cell are associated with glucose intolerance in humans and mice

Single nucleotide polymorphisms (SNPs) close to the VPS13C, C2CD4A and C2CD4B genes on chromosome 15q are associated with impaired fasting glucose and increased risk of type 2 diabetes. eQTL analysis revealed an association between possession of risk (C) alleles at a previously implicated causal SNP, rs7163757, and lowered VPS13C and C2CD4A levels in islets from female (n = 40, P < 0.041) but not from male subjects. Explored using promoter-reporter assays in β-cells and other cell lines, the risk variant at rs7163757 lowered enhancer activity. Mice deleted for Vps13c selectively in the β-cell were generated by crossing animals bearing a floxed allele at exon 1 to mice expressing Cre recombinase under Ins1 promoter control (Ins1Cre). Whereas Vps13cfl/fl:Ins1Cre (βVps13cKO) mice displayed normal weight gain compared with control littermates, deletion of Vps13c had little effect on glucose tolerance. Pancreatic histology revealed no significant change in β-cell mass in KO mice vs. controls, and glucose-stimulated insulin secretion from isolated islets was not altered in vitro between control and βVps13cKO mice. However, a tendency was observed in female null mice for lower insulin levels and β-cell function (HOMA-B) in vivo. Furthermore, glucose-stimulated increases in intracellular free Ca2+ were significantly increased in islets from female KO mice, suggesting impaired Ca2+ sensitivity of the secretory machinery. The present data thus provide evidence for a limited role for changes in VPS13C expression in conferring altered disease risk at this locus, particularly in females, and suggest that C2CD4A may also be involved

Plantes médicinales et cancer du sein (état des lieux et recommandations sur leurs utilisations)

Les traitements anticancéreux et notamment ceux pris par voie orale peuvent être à l origine d effets indésirables qui perturbent la qualité de vie de la patiente. L homéopathie, la phytothérapie, l acupuncture apparaissent parfois comme des solutions pour la patiente. Le recours à ces pratiques non conventionnelles est désigné sous le terme de médecines alternatives et complémentaires. Depuis quelques années, en cancérologie, l attrait des patientes pour ces dernières n a fait qu accroitre. Nous avons effectué une étude concernant le recours aux médecines complémentaires chez des patientes atteintes d un cancer du sein dans un service d hospitalisation de jour à l Institut de Cancérologie de l Ouest Paul Papin (ICO Paul Papin) d Angers. De plus en plus de patientes emploient des produits à base de plantes considérant que, puisqu ils sont naturels, ils sont inoffensifs. Cependant, les plantes médicinales peuvent comporter des contre-indications, interagir avec les médicaments conventionnels et même provoquer des effets secondaires et des toxicités. Nous avons élaboré des outils destinés aux patientes et aux professionnels de santé qui synthétisent l ensemble des recommandations faites sur les plantes médicinales étudiées. De plus en plus de preuves scientifiques viennent étayer l efficacité des plantes médicinales sous certaines conditions d utilisation. Malgré cela, de nombreuses lacunes restent à combler en ce qui concerne leur innocuité. C est pourquoi, dans l attente de données scientifiques complémentaires nous recommandons aux patientes qui souhaitent consommer des plantes médicinales d aborder cette utilisation avec les professionnels de santé impliqués dans leur prise en charge.Anticancer treatments including those taken orally can cause side effects interfering on the patient s life quality. Homeopathy, herbal medicine, acupuncture may be in some cases possible alternative solutions for the patient. The use of these unconventional practices is referred to as complementary and alternative medicines. In the past few years, the patients interest for these medicines is increasing. We conducted a study on the use of complementary medicine for women suffering of breast cancer. This study took place in a day-care hospital in Angers: ICO Paul Papin. More and more patients use herbal products, because they are natural and they think that they are harmless. However, medicinal plants may have contraindications and may interact with conventional drugs and even cause side effects or be toxic. We have developed tools for patients and healthcare professionals that summarize all the recommendations about medicinal plants already studied. More and more scientific evidence support the efficiency of medicinal plants under specific conditions. However many aspects have to be clarified regarding their safety. Therefore, pending further scientific data we recommend that patients who wish to consume medicinal plants get close to their healthcare professionals to check the relevance of this decision and its possible impacts.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Decreased STARD10 expression is associated with defective insulin secretion in humans and mice

Genetic variants near ARAP1 (CENTD2) and STARD10 influence type 2 diabetes (T2D) risk. The risk alleles impair glucose-induced insulin secretion and, paradoxically but characteristically, are associated with decreased proinsulin:insulin ratios, indicating improved proinsulin conversion. Neither the identity of the causal variants nor the gene(s) through which risk is conferred have been firmly established. Whereas ARAP1 encodes a GTPase activating protein, STARD10 is a member of the steroidogenic acute regulatory protein (StAR)-related lipid transfer protein family. By integrating genetic fine-mapping and epigenomic annotation data and performing promoter-reporter and chromatin conformational capture (3C) studies in β cell lines, we localize the causal variant(s) at this locus to a 5 kb region that overlaps a stretch-enhancer active in islets. This region contains several highly correlated T2D-risk variants, including the rs140130268 indel. Expression QTL analysis of islet transcriptomes from three independent subject groups demonstrated that T2D-risk allele carriers displayed reduced levels of STARD10 mRNA, with no concomitant change in ARAP1 mRNA levels. Correspondingly, β-cell-selective deletion of StarD10 in mice led to impaired glucose-stimulated Ca2+ dynamics and insulin secretion and recapitulated the pattern of improved proinsulin processing observed at the human GWAS signal. Conversely, overexpression of StarD10 in the adult β cell improved glucose tolerance in high fat-fed animals. In contrast, manipulation of Arap1 in β cells had no impact on insulin secretion or proinsulin conversion in mice. This convergence of human and murine data provides compelling evidence that the T2D risk associated with variation at this locus is mediated through reduction in STARD10 expression in the β cell

Divergent effects of liraglutide, exendin-4, and sitagliptin on beta-cell mass and indicators of pancreatitis in a mouse model of hyperglycaemia

AIMS:Glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP4) inhibitors improve glucose tolerance by still incompletely understood mechanisms. Each class of antihyperglycemic drugs has also been proposed to increase pancreatitis risk. Here, we compare systematically the effects of two widely-used GLP-1 analogues, liraglutide and exendin-4, and the DPP4 inhibitor, sitagliptin, in the mouse. METHODS:C57BL6 mice were maintained for 131 days on a normal diet (ND) or a diet comprising 60% fat (HFD) before measurements of fasting blood glucose and insulin, and intraperitoneal glucose tolerance. Beta- and alpha- cell volume, and Reg3b immunoreactivity, were measured by immunohistochemical analysis of pancreatic slices. RESULTS:Whereas liraglutide (200 µg/kg) and exendin-4 (10 µg/kg) treatment reduced body weight and/or improved glucose tolerance, sitagliptin (10 mg/kg) was without effect on either parameter. Liraglutide caused a sharp reduction in beta-cell mass in both ND and HFD mice, whereas exendin-4 exerted no effect. By contrast, sitagliptin unmasked an action of high fat diet to increase beta-cell mass. Reg3B positive area was augmented by all three agents in normal chow-fed mice, whilst sitagliptin and exendin-4, but not liraglutide, affected this parameter in HFD animals. Correspondingly sitagliptin, but not the GLP-1 analogues, increased circulating amylase levels in ND and HFD mice. CONCLUSIONS:Liraglutide improves glucose tolerance in the mouse whilst exerting relatively modest effects on pancreatitis risk. Conversely, exendin-4 and sitagliptin, at doses which exert, respectively, minor or no effects on metabolic parameters, lead to signs of pancreatitis

Local and regional control of calcium dynamics in the pancreatic islet

Ca2+ is the key intracellular regulator of insulin secretion, acting in the β-cell as the ultimate trigger for exocytosis. In response to high glucose, ATP-sensitive K+ channel closure and plasma membrane depolarization engage a sophisticated machinery to drive pulsatile cytosolic Ca2+ changes. Voltage-gated Ca2+ channels, Ca2+-activated K+ channels and Na+/Ca2+ exchange all play important roles. The use of targeted Ca2+ probes has revealed that during each cytosolic Ca2+ pulse, uptake of Ca2+ by mitochondria, endoplasmic reticulum (ER), secretory granules and lysosomes fine-tune cytosolic Ca2+ dynamics and control organellar function. For example, changes in the expression of the Ca2+-binding protein Sorcin appear to provide a link between ER Ca2+ levels and ER stress, affecting β-cell function and survival. Across the islet, intercellular communication between highly interconnected “hubs,” which act as pacemaker β-cells, and subservient “followers,” ensures efficient insulin secretion. Loss of connectivity is seen after the deletion of genes associated with type 2 diabetes (T2D) and follows metabolic and inflammatory insults that characterize this disease. Hubs, which typically comprise ~1%-10% of total β-cells, are repurposed for their specialized role by expression of high glucokinase (Gck) but lower Pdx1 and Nkx6.1 levels. Single cell-omics are poised to provide a deeper understanding of the nature of these cells and of the networks through which they communicate. New insights into the control of both the intra- and intercellular Ca2+ dynamics may thus shed light on T2D pathology and provide novel opportunities for therapy